The objective of this research program is to study the basic biological processes and mechanisms involved in activation of the fibrinolytic syytem in health and disease. These studies involve a) the plasma protein plasminogen, its various forms, and its mechanism of activation to plasmin by different activators; b) kinetic studies on plasminogen with an active site (plasminogen*); c) the mechanism of inhibition of plasmin by various types of inhibitors; d) the preparation of 1-bond and 2-bond cleaved plasmins and kinetic studies on these enzymes; e) the preparation of various types of heavy(A) and light(B) chains; f) the equimolar plasminogen-streptokinase complex, the transition forms of the zymogen and enzyme, and streptokinase, in the complex, and the development of new prototype activators; g) the phylogenetic relationships between mammalian zymogens and enzymes; and h) the development of new diagnostic methods for studying the components of the fibrinolytic system.